National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Immunol Rev. 2013 Sep;255(1):110-24. doi: 10.1111/imr.12093.
The fate of T lymphocytes revolves around a continuous stream of interactions between the T-cell receptor (TCR) and peptide-major histocompatibility complex (MHC) molecules. Beginning in the thymus and continuing into the periphery, these interactions, refined by accessory molecules, direct the expansion, differentiation, and function of T-cell subsets. The cellular context of T-cell engagement with antigen-presenting cells, either in lymphoid or non-lymphoid tissues, plays an important role in determining how these cells respond to antigen encounters. CD8(+) T cells are essential for clearance of a lymphocytic choriomeningitis virus (LCMV) infection, but the virus can present a number of unique challenges that antiviral T cells must overcome. Peripheral LCMV infection can lead to rapid cytolytic clearance or chronic viral persistence; central nervous system infection can result in T-cell-dependent fatal meningitis or an asymptomatic carrier state amenable to immunotherapeutic clearance. These diverse outcomes all depend on interactions that require TCR engagement of cognate peptide-MHC complexes. In this review, we explore the diversity in antiviral T-cell behaviors resulting from TCR engagement, beginning with an overview of the immunological synapse and progressing to regulators of TCR signaling that shape the delicate balance between immunopathology and viral clearance.
T 淋巴细胞的命运围绕着 T 细胞受体（TCR）和肽-主要组织相容性复合体（MHC）分子之间的连续相互作用。这些相互作用从胸腺开始，并延续到外周，通过辅助分子进行精细化调节，指导 T 细胞亚群的扩增、分化和功能。T 细胞与抗原呈递细胞的细胞相互作用的细胞环境在决定这些细胞对抗原接触的反应方式方面起着重要作用。CD8(+) T 细胞对于清除淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染至关重要，但病毒可能会带来一些抗病毒 T 细胞必须克服的独特挑战。外周 LCMV 感染可导致快速溶细胞清除或慢性病毒持续存在；中枢神经系统感染可导致依赖 T 细胞的致命性脑膜炎或无症状的载体状态，可通过免疫治疗清除。这些不同的结果都取决于需要 TCR 与同源肽-MHC 复合物结合的相互作用。在这篇综述中，我们探讨了 TCR 结合引起的抗病毒 T 细胞行为的多样性，首先概述了免疫突触，然后探讨了 TCR 信号转导的调节剂，这些调节剂在免疫病理学和病毒清除之间的微妙平衡中发挥作用。
